I’m late to the party, but Chad over at Uncertain Principles put out a call for great experiments/observations in our fields. Like others have said, that’s a tough one, so I thought I’d first run through some of the highlights and big breakthroughs in the fields of microbiology and infectious disease epidemiology that have made the field what it is today, and then end with the one I think is most important. Feel free to disagree.
Obviously, several early advances stand out that allowed for the field to really start to develop. In roughly chronological order:

John Snow’s contribution of linking cholera in London to a well, suggesting the disease was water-borne. His use of disease mapping, stastics, and the case/control study design to examine risk factors for disease are still essential elements of epidemiological studies.

Numerous experiments by Pasteur: showing that lactic acid fermentation is due to bacteria; that microbes don’t arise by spontaneous generation; vaccines against rabies and anthrax, demonstrating that organisms could be attenuated and made less virulent; spreading the idea that germs cause disease.

Josh Lederberg and the discovery of plasmids and the process of conjugation. This really led to the founding of the field of microbial genetics.

The discovery of restriction enzymes by Nathans, Arber, and Smith. This has been especially important in molecular epidemiology of infectious diseases–much of typing of organisms is still due to patterns produced when their DNA is cut with restriction enzymes. (Come to think of it, serotyping is another huge advance in infectious disease epi–and one that I’ve never seen touted in these kind of introductions. Something to investigate…) Restriction enzymes have also been used for gene cloning, forensic work, many other applications.

Roy Anderson and Robert May–mathematical biology, and modeling spread of infectious diseases.

If anyone’s versed in the history of medicine, you may have noticed one I missed. Rather than point to the usual suspects of Koch, Jenner, Pasteur et al., if I had to pick out experiment that has had the most impact, it would be the work of Ignaz Semmelweis. Semmelweis was a physician in Vienna in the 1840s, with an interested in “childbed fever,” a leading cause of mortality in women who’d given birth. During this time, he noticed that the mortality rate from this disease in a hospital division where medical students delivered babies was 16%, while in a division where midwives delivered them was ~2%. It was also known that childbed fever was rare when women gave birth at home. Semmelweis thought there was something the med students were doing that served to raise the rates of childbed fever in those divisions.

In 1847, Semmelweis’ friend, another physician, died due to a wound acquired while performing an autopsy. Semmelweis examined the tissues of his friend, and noticed the pathology there was similar to those in women who’d died of childbed fever. According to history, this led to his “eureka” moment: medical students performed autopsies, and midwives did not. The students must be bringing some contagious agent from the autopsy room back to the delivery room.

To test this, Semmelweis instituted a procedure, requiring students to wash their hands in a chlorine solution before entering the maternity ward. Mortality dropped dramatically, and Semmelweis extended the procedure to include surgical instruments as well. However, colleagues scoffed. Semmelweis actually lost his job, and took a position in Budapest–where he again instituted his handwashing protocol, with similar incredible results. Sadly, he died in 1865 in an asylum, disgraced.

Pasteur later identified the bacterium as Streptococcus pyogenes (group A streptococcus), and presented the example of S. pyogenes as the cause of childbed fever as support for the germ theory of disease. Thus, while Semmelweis’ ideas were not popular in his life, handwashing still remains the best way to prevent disease due to microbes, and disinfection (later built upon by Lister) has made surgery and other procedures orders of magnitude safer. Obviously, vaccination has saved millions of lives–but despite a century of intense study, vaccines are only available for precious few diseases. Studies by Koch and Pasteur have enabled us to determine microbial cause of a number of diseases and advanced the field immensely. But basic hygiene affects us–and protects us–every day, from an incredible diversity of potential pathogens. So, that’s my pick for the “greatest experiment” in my field.

In general microbiology, from the current crop (BTW, Semmelweis is one I always point out extensively; a great example of scientific inquiry).

Carl Woese, and the ribotyping method for mapping the tree of life.
Lynn Margulis, the endosymbiont theory.

From infectious disease research (somewhat tentative, I think, in some cases; I’m thinking of very recent stuff)
IVET (Mekalanos?) in vivo expression analysis
Quorum sensing (Greenberg, for one, a former colleague of yours)
Biofilms (Costerton, Greenberg, O’toole…lots of people now)
A-B subunit toxins (lots of people; I’m blanking on the name of the guy who did the ASM keynote on 04; Collier?)
Superantigens?? (probably not, but I can’t resist; look me up in pubmed to see why:)).

Ha Ha,
I figured, since you are interested in GAS, and you’re in Iowa, you probably new some folks up at U of M. Cleary’s lab was right down the hall. Good times! You’re going to do biofilms too, huh? It’s getting pretty crowded in here (ooh, that’s bad!) Cheers (no more play, gotta get the grant done…)

Re Beadle and Tatum, I’d not seen that before (of if I had, I forgot). Euraryotes, y’know…I try to stay away from them. 🙂

Paul, I did my PhD with Mike Boyle on GAS, so yeah, I’m one degree separated from pretty much everyone in that field. And a girl who was in the lab at the same time as me went on to post-doc in Cleary’s lab (now teaching at Carleton). Plus a good friend is in grad school at U of M (though in virology). So I’m pretty connected to that school, despite never having done anything there myself.

Mike, another good one. I would never have remembered his name, but we did learn about that in an advanced micro class when discussing Soviet use of phage.

T,
After Fleming you switch your choices to those
mandated by the molecularocracy. Well, I suppose.

But, how about the 1955 field trial of the polio vaccine?

And, prior to the ascendancy of the baseheads…
Ross’s proof that mosquitoes, not mal~aria, transmit malaria.
And Walter Reed and Gorgas did the same for yellow fever.
“Here, there be vectors” has to make the list.

And what about robopox’s culture medium for M. leprae?
(OK, I made that last one up. But just to remind that
there are still some big ones left to do…)

The polio vaccine is a good one. I thought about Ross/Reed etc. and considered them but left them off. Probably should have left them on there because the confirmation of vector-borne disease was indeed groundbreaking, but I didn’t want to turn it into a “every discovery ever made in micro” list. And the “molecularocracy” is admittedly my bias, as my training is in molecular biology and even my epidemiology focus is at the molecular level.